Several large-scale, randomized placebo-controlled clinical trials have demonstrated that treatment with MAO-B inhibitors leads to a symptomatic amelioration of early PD [
4‐
9]. For example, daily treatment with 10 mg selegiline (
N-Propargylmethamphetamine) in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study was associated with an improvement of about 3 points on the total Unified Parkinson's Disease Rating Scale (UPDRS) and 1.7 points on the motor subscale of the UPDRS compared to placebo after 3 months [
4]. Symptomatic effects of similar extent have been observed with the second-generation MAO-B inhibitor rasagiline (
N-Propargyl-1[R]aminoindan), which for example in the TVP-1012 in early monotherapy for PD outpatients (TEMPO) study led to an improvement of about 3 points on the total UPDRS after 3 months at a daily dose of 1 mg per day [
5]. Although it can be argued that the symptomatic effects of MAO-B inhibitors may not reach a clinically meaningful magnitude [
10] and are clearly inferior in comparison to those seen with modern dopamine agonists [
11‐
14] or even the gold-standard levodopa [
15,
16], MAO-B inhibitors may still be good candidates for initial PD treatment, since they are able to attenuate the usually mild motor symptoms during the early phase of PD, thereby facilitating the sparing of symptomatically stronger agents for later stages of the disease, when the magnitude of motor impairment ultimately requires more robust symptomatic action. Indeed, multiple studies have successfully demonstrated that early treatment with the MAO-B inhibitors selegiline or lazabemide is capable to delay the need to start with levodopa in PD patients [
4,
8,
9,
17‐
19]. Since long-term levodopa treatment is known to be associated with motor complications, the levodopa-sparing effect of MAO-B inhibitors is likely to be beneficial in the long run, although clinical studies so far failed to prove an antidyskinetic effect of MAO-B inhibition, which may have been due to wide confidence intervals in these studies [
20]. However, clinical studies have demonstrated that primary treatment with the MAO-B inhibitor selegiline reduces the incidence of motor fluctuations compared to placebo [
21] as well as to levodopa treatment [
22]. Similarly, initial monotherapy with the dopamine agonists ropinirole and pramipexole has shown to significantly decrease the incidence of dyskinesias and to a lesser extent also motor fluctuations [
23,
24]. However, this did not translate into a benefit in terms of overall function or quality of life in comparison to patients that were initially treated with levodopa [
23,
24], which somewhat argues against a general preference of dopamine agonists over other antiparkinsonian agents in the early stages of PD. In summary, initial treatment with MAO-B inhibitors provides a mild effect on motor symptoms in patients with early PD, delays the need for levodopa, reduces the incidence of motor fluctuations and may furthermore turn out advantageous from a strategic perspective, since it enables physicians to counteract emerging symptoms of early PD without already utilizing the strongest symptomatic options at the very beginning. Due to their superior symptomatic efficacy, dopamine agonists and levodopa should however be considered for initial treatment particularly in those PD patients, who require immediate and robust symptomatic control of their motor symptoms.